Nomenclature
Short Name:
TTBK1
Full Name:
Tau tubulin kinase 1
Alias:
- OTTHUMP00000016425 [Fragment]
- RP3-330M21.4
- KIAA1855
Classification
Type:
Protein-serine/threonine kinase
Group:
CK1
Family:
TTBK
SubFamily:
NA
Structure
Mol. Mass (Da):
142737
# Amino Acids:
1321
# mRNA Isoforms:
2
mRNA Isoforms:
142,737 Da (1321 AA; Q5TCY1); 69,084 Da (621 AA; Q5TCY1-2)
4D Structure:
NA
1D Structure:
3D Image (rendered using PV Viewer):
PDB ID
Subfamily Alignment
Domain Distribution:
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Acetylated:
K75.
Serine phosphorylated:
S432, S433, S456, S459, S463, S627, S630, S693, S790, S943, S944, S1200, S1246, S1248, S1253, S1259.
Threonine phosphorylated:
T12, T443, T464, T629, T1152, T1202.
Tyrosine phosphorylated:
Y169, Y695.
Distribution
Based on gene microarray analysis from the NCBI
Human Tissue Distribution
% Max Expression:
Mean Expression:
Number of Samples:
Standard Deviation:
% Max Expression:
Mean Expression:
Number of Samples:
Standard Deviation:
100
2035
15
1846
8
163
8
194
-
-
-
-
6
124
58
134
22
441
26
281
0.5
10
18
9
4
72
26
166
10
210
9
260
11
220
6
214
5
97
56
84
6
132
8
145
44
898
20
618
-
-
-
-
8
156
6
160
13
261
8
330
2
31
10
9
2
39
76
73
23
467
6
421
6
120
42
114
19
377
62
212
18
373
8
400
6
122
8
156
-
-
-
-
7
133
6
136
6
114
8
135
44
891
41
1058
12
238
6
232
11
226
6
221
11
218
6
224
20
417
28
291
21
432
12
19
5
98
10
10
0.1
2
24
0
40
818
52
703
4
78
35
83
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
35.6
48.1
99
95.8
96.1
97
-
-
-
-
-
-
35.9
48.6
91
-
-
-
89.8
91.9
90
-
-
89
-
-
-
33.9
36.9
-
-
-
75
-
-
-
-
-
66
-
-
-
-
-
-
-
-
-
-
-
34
26.1
38.2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Binding Proteins
Examples of known interacting proteins
hiddentext
| No. | Name – UniProt ID |
|---|---|
| 1 | TUBB2A - Q13885 |
| 2 | CSN1S1 - P47710 |
| 3 | CDK5R1 - Q15078 |
| 4 | MAP2 - P11137 |
| 5 | TTBK2 - Q6IQ55 |
| 6 | NUP205 - Q92621 |
| 7 | HEATR1 - Q9H583 |
Regulation
Activation:
NA
Inhibition:
NA
Synthesis:
NA
Degradation:
NA
Known Downstream Substrates
For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET
predictions.
Based on in vitro and/or in vivo phosphorylation data
| Substrate Short Name | UniProt ID (Human) | Phosphosite Location | Phosphosite Sequence | Effect of Phosphorylation |
|---|
Protein Kinase Specificity
Matrix of observed frequency (%) of amino acids in aligned protein substrate phosphosites
Matrix Type:
Predicted from the application of the Kinexus Kinase Substrate Predictor Version 2.0 algorithm, which was trained with over 10,000 kinase-protein substrate pairs and 8,000 kinase-peptide substrate pairs.
Domain #:
1
Inhibitors
For further details on these inhibitors click on the Compound Name and enter it into DrugKiNET or click on the ID's
Based on in vitro and/or in vivo phosphorylation data
| Compound Name | KD, Ki or IC50 (nM) | PubChem ID | ChEMBL ID | PubMed ID |
|---|
Disease Linkage
Comments:
TTBK1 gene variants are associated with Alzheimer's disease in Han Chinese. Transgenic mice expressing TTBK1 mutants were shown to have accelerated neurodegeneration and neuroinflammation.
Gene Expression in Cancers:
The COSMIC website notes an up-regulated expression score for TTBK1 in diverse human cancers of 298, which is 0.7-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 5 for this protein kinase in human cancers was 0.1-fold of the average score of 60 for the human protein kinases.
Mutagenesis Experiments:
Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis.
Mutation Rate in All Cancers:
Percent mutation rates per 100 amino acids length in human cancers: 0.07 % in 24728 diverse cancer specimens. This rate is the same as the average rate of 0.075 % calculated for human protein kinases in general.
Mutation Rate in Specific Cancers:
Highest percent mutation rates per 100 amino acids length in human cancers: 0.5 % in 864 skin cancers tested; 0.27 % in 1270 large intestine cancers tested; 0.22 % in 589 stomach cancers tested; 0.15 % in 1634 lung cancers tested; 0.13 % in 603 endometrium cancers tested; 0.11 % in 273 cervix cancers tested; 0.1 % in 710 oesophagus cancers tested; 0.07 % in 1512 liver cancers tested; 0.05 % in 942 upper aerodigestive tract cancers tested; 0.05 % in 1459 pancreas cancers tested; 0.05 % in 1276 kidney cancers tested; 0.04 % in 881 prostate cancers tested; 0.04 % in 833 ovary cancers tested; 0.04 % in 382 soft tissue cancers tested; 0.04 % in 1316 breast cancers tested; 0.02 % in 2082 central nervous system cancers tested; 0.02 % in 2009 haematopoietic and lymphoid cancers tested; 0.01 % in 548 urinary tract cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: A667V (5); W310L (3); S711L (3); P855S (3).
Comments:
Eleven deletions, 2 insertions and no complex mutations are noted on the COSMIC website.